Project Summary/Abstract Periodontal disease is a multifactorial inflammatory condition affecting over 64 million people in the United States that leads to alveolar bone resorption, clinical attachment loss, and, eventually, tooth loss. Current detection methods rely on mechanical assessment of pocket depth and radiographic detection of bone deterioration. By the time the disease is noted, it is already too late to fully reverse the condition. We will develop a wireless biosensor to quantify two well-established biomarkers of bone resorption, ICTP and ?-CTx, that are detectable in the gingival crevicular fluid and correlate with periodontal disease severity, onset and resolution. Both biomarkers are stable cleavage products of type I collagen ? the most abundant organic component of the bone matrix. Our central hypothesis is that implementation of a biosensor-based monitoring system for ICTP and ?-CTx will improve clinical detection of periodontal disease in high-risk patients while reducing the variability and extended time to analysis inherent to current gingival crevicular fluid analysis methods, none of which are FDA-approved for clinical use. To complete this work we will pursue three specific aims. First, we will synthesize a peptide-specific bio-recognition layer on a piezoelectric sensor that is protected from the in vivo environment using a mesoporous shell. Second, we will optimize methods for label- free, in vivo, wireless measurement of biomarker concentration based on ultrasonic powering, interrogation and telemetry in rats. Third, in addition to device development, we will generate and compile safety and efficacy data for an investigational device exemption (IDE) application to support clinical feasibility testing. When complete, we propose that our biosensor be used as a preventive strategy to accurately identify accelerated skeletal deterioration in patients at high-risk for periodontal disease, prior to a compromise in bone mass or density, thus promoting timely intervention and successful therapy. In addition to tracking disease onset in high-risk populations, accurate, longitudinal biosensor-based monitoring is needed to establish progression vs arrest of periodontal bone loss and thus determine the efficacy of therapeutic interventions. The work in this grant is consistent with the stated mission of the NIDCR to monitor the dynamics of periodontal disease, including differentiating between progressive versus arrested states and responses to treatment.